Diagnostic Breakdown: Why a HbA1c Analyzer Error Forced 55,000 Retests — What Clinicians, Regulators, and Patients Need to Know

Investigative reporting confirmed that HbA1c analyzers used by 16 NHS trusts generated positively biased results. NHS England indicated that fewer than one-tenth of NHS laboratories were affected. The manufacturer stated it worked with the UK regulator and issued three Field Safety Notices in 2024, emphasizing proper operating procedures, calibration, and awareness of a potential positive bias under specific circumstances.

Timeline highlights: first signals reached the UK regulator in April 2024; a trust-specific public alert appeared in September 2024 at Bedfordshire Hospitals (Luton & Dunstable), where 11,000 patients were recalled for repeat testing; by September 2025, retrospective reviews across affected sites identified at least 55,000 patients requiring retesting. During this period, NHS England observed about 10,000 more type 2 diabetes diagnoses in 2024 (roughly 4% above expected), plausibly influenced by biased HbA1c values.

Experts judge the risk of serious clinical harm to be low, but the human and system burdens are substantial. Some patients were started on glucose-lowering therapies such as metformin, then advised to stop, generating distress, side effects, and avoidable follow-up. Primary care and specialty services absorbed surges in retest appointments, medication reviews, and counseling, while laboratories replaced or recalibrated devices, tightened quality checks, and coordinated communication cascades.

HbA1c reflects the proportion of hemoglobin irreversibly glycated over the prior 8–12 weeks and anchors both diagnosis and longitudinal monitoring of diabetes. Common analytical methods include cation-exchange high-performance liquid chromatography (HPLC), immunoassays, enzymatic assays, boronate affinity chromatography, and capillary electrophoresis. Each has distinctive operating principles and vulnerability to interferences.

Two recurrent sources of method-dependent error are hemoglobin variants and elevated fetal hemoglobin (HbF):

- Hemoglobin variants: Multicenter work comparing HPLC with whole-blood enzymatic assays across 33 variants shows clinically relevant interference in certain settings, with enzymatic assays notably challenged by the inability to flag variants. Chromatographic and electrophoretic methods may reveal variant peaks or patterns that trigger reflex review.

- Fetal hemoglobin (HbF): Comparative studies indicate that elevated HbF can bias results across platforms; a recent comparison against the IFCC reference method reported significant negative bias that worsened as HbF increased across boronate affinity, immunoassay, enzymatic, HPLC, and capillary electrophoresis systems.

The UK episode centered on a reported positive bias, but the broader literature shows HbA1c bias can be positive or negative depending on both the assay design and sample biology. Understanding method-specific limitations, the prevalence of variants in the tested population, and how analyzers flag anomalies is essential for both laboratory selection and clinical interpretation.

For recalled patients, the priority is diagnostic confirmation and safe course correction:

- Reconfirm diagnosis: Repeat HbA1c on a verified platform, with the method noted on the report and quality-control status documented. If the clinical picture conflicts with repeat HbA1c — or if hemoglobin variants or elevated HbF are suspected — corroborate with plasma glucose-based testing (fasting plasma glucose or an oral glucose tolerance test) to anchor decisions in independent measures.

- Medication stewardship: Where glucose-lowering therapy (e.g., metformin) was initiated solely on a potentially biased HbA1c, supervise deprescribing with a clear rationale and documentation.

- Safety-netting: Counsel on warning signs of hyperglycemia and — for those exposed to medicines that reduce glucose — symptoms of hypoglycemia and when to seek urgent care. Provide unambiguous retest intervals and follow-up plans.

For ongoing care, align therapeutic targets to confirmed measures and avoid both overtreatment from spurious elevations and therapeutic inertia when genuine hyperglycemia is present. If hemoglobin variants or high HbF are likely, prefer methods with robust interference profiles or use alternative glycemic assessments when appropriate (for example, serum fructosamine in select scenarios or patterns from validated continuous glucose monitoring).

UK oversight emphasized post-market vigilance. From April 2024, the regulator engaged with the manufacturer, which issued three Field Safety Notices that year. NHS England indicated fewer than 10% of laboratories used the implicated systems; affected sites replaced or recalibrated devices and coordinated retesting with primary care and hospital clinics.

International parallels demonstrate similar risk vectors. Recent device enforcement actions in the United States include: a Class II recall of a point-of-care HbA1c system due to mismatched cartridge and analyzer codes with potential for inaccurate results; a Class II recall of a laboratory HbA1c reagent kit citing potential for unexpected positive or negative results; and a Class II recall of an HbA1c reagent kit confirmed to display a positive bias without alerting users. These actions, while varied in root cause, underscore how small analytical shifts can precipitate clinical misclassification.

Quality assurance takeaways: strengthen internal quality control and external quality assessment triggers to detect drift or bias earlier; implement variant detection or reflex workflows when method limitations are known; and ensure rapid, precise communication between laboratories, clinicians, and patients during alerts. Reporting formats that display the analyzer method, software/reagent versions, and known interferences support safer interpretation.

For clinicians:

- Identify patients whose HbA1c was measured on impacted analyzers; prioritize retests for those newly diagnosed or started on therapy in 2024–2025.

- Use corroborative testing (fasting plasma glucose/OGTT) when HbA1c reliability is in doubt; document analyzer method and potential interferences.

- Communicate that immediate harm risk is low but clarity is essential; supervise deprescribing and provide safety-netting and scheduled follow-up.

For patients:

- Attend recall testing and do not stop medications unless instructed by your clinician.

- Seek care if you have symptoms of very high or very low blood sugar.

- Expect that many initial management steps emphasize lifestyle measures and monitoring while results are confirmed.

For laboratories:

- Validate corrective actions and document post-remediation performance (IQC/EQA trends, drift checks, stability data).

- Show method notes/flags on reports and maintain reflex pathways for suspected variants or high HbF.

- Maintain escalation plans for device/reagent alerts, including clinician and patient communication templates.

Method selection should reflect population context. Laboratories serving regions with higher hemoglobin variant prevalence benefit from technologies that display variant peaks or provide flags, enabling reflex confirmation before results reach clinicians. For point-of-care HbA1c deployments that expand access, ensure robust operator training, lot-level traceability, and rapid response plans for alerts.

Transparency belongs on every HbA1c report: method and versioning, known interferences, flags, and any reflex actions taken. Education for primary care and nursing staff on method-specific pitfalls helps prevent misinterpretation and supports using the right test for the right patient.

Post-market surveillance should be nimble and data-driven. Clear, timely field safety communications from manufacturers and regulators that include clinical context and step-wise mitigation shorten the interval from signal to action, minimizing downstream impact and preserving trust.